Paradigms of Wound Healing and Fibrosis in the Eye

眼睛伤口愈合和纤维化的范例

基本信息

  • 批准号:
    9790961
  • 负责人:
  • 金额:
    $ 52.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-30 至 2022-05-31
  • 项目状态:
    已结题

项目摘要

Abstract/Project Summary Immune privilege of the eye results from the need to keep vasculature from the central light path where it would impair vision. Therefore, organs and tissues of the eye like the cornea, have developed alternative mechanisms of immune surveillance to protect them and in response to injury or tissue pathogenesis. In the CNS, novel immune surveillance adaptations have been discovered for protection and repair that demonstrate a state of immune quiescence. In the cornea, which can tolerate foreign antigens, there are immune cells that surveille it in the peripheral regions of the cornea, the aqueous humor, and the tears. The lens has remained an enigma in terms of immune surveillance and protection. We now show that, like other tissues, the lens has developed mechanisms of immune surveillance to protect it throughout a lifetime and to respond to stresses and injury while maintaining its transparency. Since dysregulation of immune surveillance is tightly linked to development of fibrosis, it is possible that the immune cells that associate with the lens may be an unexplored cause of cataract and posterior capsule opacification (PCO). We have discovered resident immune cells (β2 integrin/CD45+) in the lens, that are activated upon mock cataract surgery and have essential functions in regenerative repair of the wound area. These cells are susceptible to being diverted from this role, and induced to acquire a myofibroblast phenotype, the cell type that underlies fibrotic PCO. The resident immune cells first appear in the lens during development, delivered by the tunica vasculosa, a vasculature that surrounds the developing lens; however, this vasculature degenerates after birth. It was assumed that there are no active sources of immune cells that could surveille and protect the adult lens during homeostasis and in response to stress, injury, or pathogenesis. However, we discovered that in response to lens dysgenesis (N-cad∆lens mice) or corneal debridement wounding, an extrinsic immune surveillance mechanism is activated resulting in the recruitment of immune cells to the lens. These immune cells move between the ciliary body and the lens across the ciliary zonules that connect them, in the absence of a vasculature. Over time, these immune cells can acquire a myofibroblast phenotype and lead to lens opacity. Studies of eyes from these N-cad∆lens mice also revealed that there is an immune response to lens dysgenesis in the central cornea, vitreous, and retina. We will build on these findings in three specific aims expected to elucidate how extrinsic immune cells are able to travel to the lens, how the immune system is activated to protect the lens in response to corneal injury and to protect the cornea in response to lens dysgenesis, and how immune cells that surveille the lens in response to its damage/pathogenesis, or that of another tissue, may lead to cataract and PCO.
摘要/项目摘要 眼睛的免疫特权是由于需要使脉管系统远离中心光路, 会损害视力因此,眼睛的器官和组织,如角膜,已经发展出替代性的 免疫监视机制,以保护他们和响应损伤或组织发病机制。在 CNS,已经发现了用于保护和修复的新的免疫监视适应, 表现出免疫静止状态。在角膜中,可以耐受外来抗原, 免疫细胞在角膜、眼水和眼泪的周边区域监视它。的 透镜在免疫监视和保护方面仍然是一个谜。我们现在表明,像其他 透镜已经发展了免疫监视机制,以在整个生命周期中保护它, 对压力和伤害做出反应,同时保持其透明度。由于免疫功能失调, 监视与纤维化的发展密切相关,与纤维化相关的免疫细胞可能 透镜可能是白内障和后囊膜混浊(PCO)的一个未探索的原因。 我们在透镜中发现了常驻免疫细胞(β2整合素/CD 45+), 模拟白内障手术,并在伤口区域的再生修复中具有重要功能。这些细胞 容易从这种作用转移,并诱导获得肌成纤维细胞表型,细胞类型 导致纤维化性PCO常驻免疫细胞首先出现在发育过程中的透镜中, 通过图尼卡血管膜,围绕发育中的透镜的脉管系统;然而,该脉管系统 出生后退化。人们认为,没有活跃的免疫细胞来源可以监视 并在体内平衡期间和响应于应激、损伤或发病机制保护成人透镜。然而,在这方面, 我们发现 在对透镜发育不全(N-cad晶状体透镜小鼠)或角膜清创损伤的应答中, 监视机制被激活,导致免疫细胞募集到透镜。这些免疫 细胞在睫状体和透镜之间移动穿过连接它们的睫状小带, 血管系统。随着时间的推移,这些免疫细胞可以获得肌成纤维细胞表型,并导致透镜 不透明对来自这些N-cad晶状体透镜小鼠的眼睛的研究还揭示了对透镜存在免疫应答 中央角膜、玻璃体和视网膜发育不全。 我们将以这些发现为基础,以三个具体目标来阐明外源性免疫细胞是如何 能够到达透镜,免疫系统如何被激活以保护透镜,以应对角膜炎。 损伤和保护角膜以应对透镜发育不全,以及监视透镜的免疫细胞如何 响应于其损伤/发病机理,或另一组织的损伤/发病机理,可能导致白内障和PCO。

项目成果

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A. Sue Menko其他文献

Shared Phenotypes of Immune Cells Recruited to the Cornea and the Surface of the Lens in Response to Formation of Corneal Erosions
角膜糜烂形成时被募集到角膜和晶状体表面的免疫细胞的共有表型
  • DOI:
    10.1016/j.ajpath.2025.01.006
  • 发表时间:
    2025-05-01
  • 期刊:
  • 影响因子:
    3.600
  • 作者:
    Phuong M. Le;Sonali Pal-Ghosh;Mary Ann Stepp;A. Sue Menko
  • 通讯作者:
    A. Sue Menko

A. Sue Menko的其他文献

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{{ truncateString('A. Sue Menko', 18)}}的其他基金

Paradigms of maintaining anterior segment homeostasis
维持眼前节稳态的范例
  • 批准号:
    10600479
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    8328686
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    8786860
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    9127959
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    10174935
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    8161860
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    8516041
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Paradigms of Wound Healing and Fibrosis in the Eye
眼睛伤口愈合和纤维化的范例
  • 批准号:
    9334585
  • 财政年份:
    2011
  • 资助金额:
    $ 52.69万
  • 项目类别:
Confocal Core Facility for Vision Researchers
视觉研究人员的共焦核心设施
  • 批准号:
    6653653
  • 财政年份:
    2003
  • 资助金额:
    $ 52.69万
  • 项目类别:
Tyrosine Phosphorylation in Lens Cell Differentiation
晶状体细胞分化中的酪氨酸磷酸化
  • 批准号:
    6610744
  • 财政年份:
    2003
  • 资助金额:
    $ 52.69万
  • 项目类别:

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